Sins of the father may rescue the son

Cocaine use in male rats induces heritable changes which result in decreased cocaine-seeking behavior in their male offspring, reports a paper published online this week in Nature Neuroscience.

R. Christopher Pierce and colleagues found that male rats that were allowed to self-administer cocaine for 60 days prior to mating produced male offspring who were more resistant to addictive behavior. This effect was not observed in the female offspring, however.

Increased expression of a gene called brain-derived neurotrophic factor (or BDNF) in a region of the brain called the medial prefrontal cortex (mPFC) is known to reduce drug-seeking behavior in rodents and, indeed, the authors found that these male offspring express higher levels of BDNF in the mPFC. Analysis of the BDNF gene in these animals revealed increased acetylation (a chemical change to the gene which permits greater expression). This increased acetylation of the BDNF gene could also be found in the sperm of the fathers, suggesting that this change occurred in response to cocaine use and was transmitted to their sons.

These findings contradict much human epidemiological data which suggests that parental cocaine use leads to increased probability of drug use in offspring. However, this work serves to highlight the fact that a more careful evaluation of the biological versus environmental effects of drug abuse is necessary to fully understand the heritability of addiction.